This is a 4-year study that uses a 10-week telephone based cognitive behavioral stress management intervention (T-CBSM) to illuminate neuroimmune mechanisms underlying the effects of stress and stress management on physical health status and immune regulation in individuals with chronic fatigue syndrome (CFS) relative to participants receiving a health promotion telephone (T-HP) intervention. CFS is characterized by physical symptoms which bring about severe limitations in lifestyle behaviors and vocational activities. Associated symptoms include debilitating fatigue, low grade fever, lymph node pain and tenderness, cognitive difficulties, and mood changes. There is growing evidence that CFS patients may also show abnormalities in HPA axis functioning and on several indices of immune functioning. Chronic stress is also associated with a flattened diurnal secretion pattern for cortisol. An inability to maintain regulation in the HPA axis may contribute to the pathophysiology of CFS via diminished control of pro-inflammatory cytokines and associated physical symptoms related to chronic immune activation and inflammation. Given the debilitating nature of CFS, we propose to deliver the T-CBSM intervention through a telecommunications system (i.e. Telecare) designed to enhance access to formal and informal care for a population that may have difficulty accessing traditional psychotherapeutic settings. In our prior work with individuals with CFS, we have shown that individuals in a structured group CBSM intervention report significantly improved quality of life, perceived stress, fatigue, memory, muscle pain, and post-exertional malaise compared to individuals in the control condition. The Telecare system has been successful in delivering a supportive intervention for older caregivers of dementia patients. This study is novel in expanding our prior work to individuals with CFS who have reported difficulty participating in structured groups due to physical burden. The study design is a 2 X 3 randomized experimental design with group (T-CBSM, n=60 vs. T-HP, n=60) as the between-group factor, and time (Pre-intervention, Post-intervention and 6 month follow-up) as the within-group factor. Our primary objective is to evaluate the extent to which a T-CBSM intervention Aimed at building skills in anxiety reduction, distress tolerance, stressor appraisals, and adaptive coping strategies may improve physical health status and immune regulation in CFS by modulating neuroimmune interactions.